(BQ) Part 1 book Neurocritical care A guide to practical management presentation of content: Brain injury and dysfunction The critical role of primary management, monitoring the injured brain, the secondary management of traumatic brain injury, critical care management of subarachnoid hemorrhage, central nervous system infections, cervical spine injuries,...
www.ebook3000.com Competency-Based Critical Care www.ebook3000.com Series Editors John Knighton, MBBS, MRCP, FRCA Consultant Intensive Care Medicine & Anaesthesia Portsmouth Hospitals NHS Trust Portsmouth UK Paul Sadler, MBChB, FRCA Consultant Critical Care Medicine & Anaesthesia Queen Alexandra Hospital Portsmouth UK Founding Editor John S.P Lumley Emeritus Professor of Vascular Surgery University of London London UK and Honorary Consultant Surgeon Great Ormond Street Hospital for Children NHS Trust (GOSH) London UK Other titles in this series Renal Failure and Replacement Therapies edited by Sara Blakeley www.ebook3000.com John P Adams • Dominic Bell • Justin McKinlay (eds.) Neurocritical Care A Guide to Practical Management www.ebook3000.com Editors John P Adams The General Infirmary at Leeds Great George Street Leeds LS1 3EX United Kingdom John.Adams@leedsth.nhs.uk Dominic Bell The General Infirmary at Leeds Great George Street Leeds LS1 3EX United Kingdom dominic.bell@leedsth.nhs.uk Justin McKinlay The General Infirmary at Leeds Great George Street Leeds LS1 3EX United Kingdom justin.mckinlay@leedsth.nhs.uk ISSN 1864-9998 e-ISSN 1865-3383 ISBN 978-1-84882-069-2 e-ISBN 978-1-84882-070-8 DOI 10.1007/978-1-84882-070-8 Springer London Dordrecht Heidelberg New York British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Control Number: 2009931330 © Springer-Verlag London Limited 2010 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licenses issued by the Copyright Licensing Agency Enquiries concerning reproduction outside those terms should be sent to the publishers The use of registered names, trademarks, etc., in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) www.ebook3000.com John Adams dedicates this book to his wife Kate to compensate for neglect of his responsibilities as husband and father The families of his fellow editors did not specifically notice or comment and for this we are grateful www.ebook3000.com Preface Brain injury is a worldwide leading cause of mortality and morbidity and requires early and appropriate management to minimize these adverse sequelae Despite such needs, access to specialist centers is limited, forcing both immediate and secondary care of these patients onto generalist staff These responsibilities are made more problematical by differences in patient management between and even within specialist centers, due in part to an insufficient evidence-base for many interventions directed at brain injury This book is borne out of the above observations and is targeted at emergency and acute medicine, anesthetic and general intensive care staff caring for brain injury of diverse etiology, or surgical teams responsible for the inpatient care of minor to moderate head trauma Although explaining the various facets of specialist care, the book is not intended to compete with texts directed at neurosciences staff, but aims to advise on optimal care in general hospitals, including criteria for transfer, by a combination of narrative on pathophysiology, principles of care, templates for documentation, and highly specific algorithms for particular problems It is intended that the content and structure can form the basis of guidelines and protocols that reflect the needs of individual units and that can be constantly refined Our ultimate goal is to promote informed, consistent, auditable, multidisciplinary care for this cohort of patients and we hope that this text contributes to that process vii www.ebook3000.com Acknowledgments We are indebted to our fellow authors who have not only made this book possible, but have approached the task with enthusiasm All understand and endorse the importance of clear, comprehensive, evidence-based, and consistent advice in the support of colleagues caring for these patients outside the regional center We are also grateful for the observations of colleagues responsible for the eventual rehabilitation of these patients, mainly that even minor reductions in neurological deficit by early and appropriate care, can have a significant impact on quality of life, with proportional benefit not only for the patient, but family, health and social care institutions, and society These observations justify the book and warrant implementation of the contained principles Finally, we thank Melissa Morton in the UK and Robin Lyon in New York for all their help and support in bringing this book to publication ix www.ebook3000.com Contents Chapter Brain Injury and Dysfunction: The Critical Role of Primary Management M.D Dominic Bell Chapter Monitoring the Injured Brain Simon Davies and Andrew Lindley Chapter The Secondary Management of Traumatic Brain Injury Dominic Bell and John P Adams 19 Chapter Critical Care Management of Subarachnoid Hemorrhage Audrey C Quinn and Simon P Holbrook 33 Chapter Central Nervous System Infections Abigail Walker and Miles Denton 43 Chapter Cervical Spine Injuries John P Adams, Jake Timothy, and Justin McKinlay 51 Chapter Recent Advances in the Management of Acute Ischemic Stroke Ahamad Hassan 61 Chapter Seizures on the Adult Intensive Care Unit Morgan Feely and Nicola Cooper 69 Chapter Non-Neurological Complications of Brain Injury John P Adams 77 Chapter 10 Acute Weakness in Intensive Care Louise Barnes and Michael Vucevic 89 Chapter 11 Coma, Confusion, and Agitation in Intensive Care Matthew Clark and Justin McKinlay 97 xi www.ebook3000.com xii Contents Chapter 12 Death and Donation in Critical Care: The Diagnosis of Brainstem Death 105 Paul G Murphy Chapter 13 Death and Donation in Critical Care: Management of Deceased Organ Donation 113 Paul G Murphy Chapter 14 Imaging the Brain-Injured Patient 121 Tony Goddard and Kshitij Mankad Chapter 15 Ethical Dilemmas Within Intensive Care 137 M.D Dominic Bell Appendices 145 Index 173 www.ebook3000.com 54 As a pure piston contracting downward to increase intrathoracic volume By flattening, it functions as a piston, but one governed by Laplace’s law By interacting through the zone of apposition with the lower ribcage, the abdominal contents act as a fulcrum to expand the lower ribcage Following cervical cord injury, intercostal muscle function is lost, with consequent failure of AP expansion of the ribcage More importantly, without intercostals muscle contraction, as the diaphragm contracts the chest wall is sucked in, reducing its efficiency and causing paradoxical chest wall movement Lost innervation to the lower thoracic segments causes the diaphragm to start at a more caudal position This increases the radius of curvature and, from Laplace, reduces transdiaphragmatic pressure on contraction As the diaphragm descends, due to lost abdominal muscle tone the abdominal contents are pushed out and cannot provide the fulcrum needed to expand the lower chest The lower ribcage is pulled in whilst the abdominal content are pushed out, resulting in the “see-saw” pattern of respiration often seen With increased intra-abdominal compliance, the diaphragm is pulled down by the weight of the abdominal content, especially when upright, dramatically reducing the zone of apposition Lung compliance is also reduced, mainly due to a loss of gas containing alveoli secondary to atelectasis Reduced lung volume compounds the problem by reducing surfactant production Muscles of Expiration Loss of abdominal muscle activity results in a decrease in maximal expiratory force and a reduced ability to cough, clear secretions, and protect the airway Atelectasis increases the load placed on already compromised muscles of inspiration and V/Q mismatch occurs Alveolar hypoventilation is inevitable and respiratory failure very common Principles of Respiratory Care Spontaneously breathing patients with SCI require close observation and aggressive management including: J.P Adams et al · Close monitoring of respiratory muscle strength and ability to cough and clear secretions · Intensive chest physiotherapy, including early use of BIPAP and cough assist devices (mechanical insufflators–exsufflator devices which alternate positive and negative airway pressures to generate a cough) · Nurse in the supine position Some of the physiological changes caused by SCI can be lessened by maintaining patients in a supine position When supine, the weight of abdominal contents pushes the diaphragm higher into the chest, increasing apposition with the ribcage, reducing diaphragm radius of curvature and helping to restore the fulcrum effect lost with higher abdominal compliance Supine values of FVC and FEV1 are larger compared with values when seated, down to an injury level of T1 Binding the abdomen when patients are sat upright helps diaphragm function · Humidified oxygen and mucolytic therapy, for example, nebulized N-acetylcysteine, oral carbocisteine, and nebulized dornase alfa · Adequate hydration and nutrition · Prevention of pressure sores, by frequent turning, and prophylaxis for venous thromboembolism (VTE) Ventilation and Weaning Where there is an associated lung injury for example, pulmonary contusions or an underlying lobar infection then traditional lung protective ventilation should be employed to prevent ventilator associated lung injury Weaning from mechanical ventilation can take weeks or months, and it is essential that patients are prevented from becoming tired during the weaning process Normally, it should only be embarked upon once active pulmonary pathology has resolved (i.e once FiO2 is less than 30%), and little progress is often made until flaccid intercostal muscles develop some spasticity Weaning strategies include conventional SIMV weaning, pressure support weaning and “T-piece” or “Sprint” weaning Tracheostomies are usually essential in weaning patients, but thought should be given to facilitating speech – using fenestrated tubes, having periods where cuffs are left down to allow air to pass upward through the vocal cords, or using a one- way speaking valve (for example, a Passy-Muir valve) 6. Cervical Spine Injuries Circulation Hypotension is common after SCI and must be treated aggressively Causes include hypovolemia, neurogenic shock, and the effects of sedation and positive pressure ventilation The terms spinal shock and neurogenic shock are often confused Spinal shock refers to the acute phase following spinal cord disruption where descending autonomic pathways are interrupted, resulting in loss of all somatic and reflex activity below the level of the injury It is seen in about 50% of cases and symptoms include flaccid paralysis, priapism, and loss of bowel and bladder function It usually starts to resolve within the first 48 h In the weeks after SCI, flaccid paralysis is replaced with spastic paralysis and a gradual improvement in respiratory function is often seen Neurogenic shock is characterized by hypotension (disrupted sympathetic outflow), bradycardia (unopposed vagal tone) and hypothermia It is more commonly seen with injuries above T6 and needs to be distinguished from spinal shock and hypovolaemic shock, the latter being more often associated with tachycardia Neurogenic shock needs careful treatment with fluid resuscitation, vagolytic agents (e.g., atropine 0.3–0.6 mg) and pressor agents such as noradrenaline (norepinephrine) or phenylephrine (Neo-Synephrine) on an intensive care unit with invasive hemodynamic monitoring Spinal cord blood flow is around 50 mL/100g/ min and is under autoregulatory control between mean arterial pressures of 60-150 mmHg It is also dependent on intrathecal pressure and in certain situations (e.g., thoracic aneurysm surgery) spinal cord perfusion can be improved by draining CSF Autoregulation can be disrupted in traumatic SCI; hypotension and hypoxia must be avoided as they may result in further ischemic damage to the cord Similarly, severe hypertension and hyperemia may worsen cord edema and lead to further secondary injury Keep MAP ~80–90 mmHg Like the brain, the spinal cord is susceptible to secondary insults after the primary injury Hypoxia and hypotension must be avoided as they may lead to further ischemic damage and a worse neurological outcome 55 Neurogenic pulmonary edema may be associated with SCI The intense autonomic discharge after injury leads to marked vasoconstriction and an increase in afterload, with blood being shunted from the systemic to the pulmonary circulations There is disruption of the pulmonary capillary endothelium, which leads to alveolar hemorrhage and pulmonary edema Myocardial stunning may also occur and the patient may appear moribund Treatment consists of ventilation with PEEP, careful fluid resuscitation (guided by invasive hemodynamic monitoring), and titration of inotropes and vasopressors This has been discussed in detail in Chap.9 Neurology A thorough neurological assessment should document the precise level of sensory and motor deficit (including any evidence of sacral sparing), and record details about tendon reflexes and sphincter tone Despite optimal treatment, the injury level may rise in the hours or days after the initial event, so repeated neurological examination is mandatory Definitions: · Complete injury: loss of all sensory and motor function below the lesion, including loss of control of bowel and bladder function · Incomplete injury: Some ascending or descending tracts are spared Examples include: · Brown-Séquard syndrome: cord hemisection with ipsilateral hemiplegia and contralateral pain and temperature-sensory deficits · Central cord syndrome: usually follows a hyperextension injury with a greater loss of motor function in the arms than in the legs, and a variable amount of sensory loss below the level of the injury · Sacral sparing: this is a significant prognostic sign as it is often associated with better outcomes and recovery after SCI Autonomic hyper-reflexia: In the chronic phase after SCI, many patients with lesions above T6 will exhibit exaggerated responses to triggers such as bladder or bowel distension This is characterized by hypertension, bradycardia, and vasodilatation above the level of the lesion If left untreated, complications including stroke, pulmonary edema, and myocardial infarction can occur 56 The stimulus must be removed promptly (e.g., bladder catheterization or bowel evacuation) and occasionally the condition will warrant drug treatment with a rapidly acting vasodilator (e.g., sublingual nifedipine or GTN) Radiology Traditionally, all patients with suspected cervical spine trauma will have the three standard plain X-rays consisting of lateral, anterior–posterior and open-mouth odontoid peg views In the intubated patient the latter will be replaced by a submental projection When stable, the patient will also have thin CT cuts of the occipito–atlanto-axial region and the C7/T1 region Modern radiological techniques allow for very rapid helical CT scans of the cervical spine which, increasingly is removing the need for the three plain views The combination of good-quality plain films and focused CT slices excludes over 99% of significant cervical spine trauma in adults If pathology is discovered, the patient will probably require an MRI scan to plan further treatment and further imaging of the whole spine to look for additional damage Other imaging modalities J.P Adams et al such as flexion–extension fluoroscopy should not be done without expert advice, and only when other imaging has been negative (see Fig. 6.1) Other Injuries Patients with cervical spine trauma are likely to have other injuries and a thorough assessment is required High spinal injuries may mask intraabdominal injury, and further imaging or a diagnostic peritoneal lavage should be performed if this is suspected Types of Cervical Spine Fractures Injuries to the C1–2 complex are associated with a lower incidence of serious neurological injury than injuries lower down (C3–7), possibly as a result of increased space for the cord at the higher level Atlanto–occipital disruption, however, is associated with a higher risk of immediate fatality due to disruption of brainstem function Those who survive will need stabilization by either nonsurgical or surgical techniques (see Fig. 6.2) Cervical spine fractures are often described by their mechanism of injury: Figure 6.1. The diagnosis of acute injury can be difficult in the presence of the degenerative spine Flexion-extension views demonstrate stability This X-ray shows what looks like an acute slip at C4/5 but the flexion-extension views demonstrate that this is old and stable 6. Cervical Spine Injuries 57 · Hyperflexion: Excessive neck flexion in the Saggital plane (e.g., diving in to shallow water, trampoline accidents) resulting in disruption of the posterior ligament, for example, flexion-burst fracture (Fig. 6.3a), unilateral facet (Fig. 6.3b), or bilateral facet dislocation (Fig. 6.3c) · Hyperextension: Excessive neck extension in the Saggital plane (e.g., hitting the dash board in a motor vehicle accident resulting in a Hangman’s fractures – Fig. 6.4) · Axial compression: Excessive force applied directly downward through the skull may result in compression fractures (e.g., Jefferson fracture – burst fracture of C1 – Fig. 6.5) Stability: The stability of the cervical spine has three determinants: Figure 6.2. Posterior occipito-cervical fixation with bone graft to treat an unstable fracture in the upper cervical spine Biomechanical factors, which take into account the disc, vertebral body, ligaments, and facet joints There are different biomechanical concepts, a widely recognized example being the three concept model of Denis Radiological factors, which are determined by abnormal radiological features and abnormal movements on dynamic films Clinical factors, which takes the clinical features in conjunction with the radiological findings Figure 6.3. (a) Flexion injury after diving in to a shallow pool Lateral view shows a burst fracture of C6 (red arrow) (b) Unifacetal fractures are potentially unstable and the management varies substantially They are characterized by < 50% of vertebral body slip (c) Bifacetal fracture of C5/6 where > 50% of the vertebral body has slipped forward This is a highly unstable fracture that requires urgent stabilization J.P Adams et al 58 The Importance of Clearing the Cervical Spine on the ICU Unconscious patients in the Intensive Care Unit will often have their spine immobilized for prolonged periods of time, mainly because of concerns about adequacy of plain films and the inability to assess the patient’s neurology There is understandable concern about displacing potentially unstable spinal injuries with subsequent neurological deficit However, the complications of prolonged immobilization are often understated and underestimated (see Table 6.1) As previously stated, good-quality plain films combined with focused CT slices will detect over 99% of serious cervical spine injuries Imaging should be interpreted by a senior radiologist and after appropriate documentation by the orthopedic or neurosurgical specialist, the collar should be removed The patient should then be closely monitored for any subsequent spinal pain, weakness, or paresthesia Figure 6.4. Hangman’s fracture (hyperextension injury) showing anterior dislocation of C2 body with C2 pars interarticularis fractures (red arrow) Fluid Balance Careful attention is required to avoid excessive volume loading and tissue edema, particularly where there is an associated lung injury Spinal shock will result in bladder distension, but in the longer term intermittent catheterization may be feasible as reflex emptying of the bladder develops The Role of Steroids Steroids are not universally used in the treatment of acute SCI, and administration is dictated by local policy Figure 6.5. Jefferson fracture (axial compression fracture) of the bony ring of C1 (unstable) This open mouth view shows bilateral offset of the C1 lateral masses on C2 (white arrows) In the acute setting stability may be difficult to confirm, especially in the unconscious patient, and therefore patients should be treated as unstable until they can be properly assessed Table 6.1 Complications of prolonged spinal immobilization • P ressure sores: common (especially after 48 h ) and potentially devastating • Venous obstruction, increased ICP • Potential airway and central venous access difficulties • Restricted physiotherapy: increased risk of VAP and VTE • Problems with enteral nutrition, reflux and aspiration • Oral hygiene (bacteraemia, sepsis) • Cross-infection (at least five people required for log-roll) 6. Cervical Spine Injuries Following the NASCIS II (1990) and NASCIS III (1997) studies, high-dose methylprednisolone was routinely used in acute SCI However, in both studies the drug only had an impact when given early (220 mmHg, diastolic >120 mmHg) or evidence of aortic dissection Acute lowering of blood pressure could increase tissue injury by reducing cerebral perfusion, although one small study showed benefit with candesartan (Schrader et al 2003) A recent study examining the A Hassan use of insulin to maintain very tight glycemic control in acute stroke (GIST), found no benefit for this approach, although the study was underpowered because of slow recruitment (Gray et al 2007) Arterial Reperfusion: Systemic Thrombolysis Thrombolytic treatment for ischemic stroke using intravenous recombinant tissue plasminogen activator (r-tPA) 0.9 mg/kg is established in North America, and has more recently been licensed in Europe and Australasia The treatment aims to restore perfusion to vulnerable penumbral tissue by enhancing clot fibrinolysis However, there is a risk of reperfusion resulting in symptomatic hemorrhage into areas of infarction or at other sites Evidence for the efficacy of r-tPA has been provided by five moderately large randomized controlled trials (The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group 1995; Hacke et al 1995, 1998; ; Clark et al 1999, 2000; Fig. 7.1a) The pivotal trial was the NINDS r-tPA trial (The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group 1995) which demonstrated that thrombolytic treatment administered within 3 h of stroke was more likely to lead to a full neurological recovery from stroke compared to placebo, without an excess risk of mortality The absolute risk reduction was 12% equating to extra patient fully recovered for every treated The risk of symptomatic hemorrhage in the study was 6% The NINDs study was unique in that patients were treated very quickly, whereas in the other trials there were longer time windows, up to 6 h A subsequent pooled analysis of trial data has suggested that the risk–benefit ratio of treatment is more favorable if undertaken within 3 h (Fig. 7.1b), and the earlier the treatment administered, the greater the benefit (Hacke et al 2004) A post-marketing surveillance study designed to ensure safe usage of the drug in clinical practice, Safe Implementation of Thrombolysis in Stroke MOnitoring STudy (SITS-MOST) found similar rates of intracerebral hemorrhage and lower mortality rates in comparison with results from the above-pooled randomized control trials (Wahlgren et al 2007) Table 7.1 lists some of the inclusion and exclusion criteria for thrombolysis using r-tPA 7. Recent Advances in the Management of Acute Ischemic Stroke a Study Year Treatment n/N 63 Control n/N OR (95% CI) OR (95% CI) NINDS 1995 122/312 81/312 1.82(1.30 to 2.54) ECASS I 1995 112/313 90/307 1.34 (0.96 to 1.88) ECASS II 1998 165/407 143/376 1.11 (0.83 to 1.48) ATLANTIS B 1999 128/307 124/306 1.05 (0.76 to 1.45) ATLANTIS A 2000 33/71 35/71 0.89 (0.46 to 1.72) 473/1372 125 (1.07 to 1.46) Total 560/1410 0.2 0.5 Favours control Favours treatment Adjusted odds ratio b OR estimated by model 95% CI for estimated OR 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 60 90 120 150 180 210 240 270 300 330 360 OTT (min) Figure 7.1. (a) Overview of five major trials investigating the role of thrombolysis, using the endpoint of near or complete functional recovery (mRS or 1) With permission from BMJ publishing group, Muir KW, Medical management of stroke J Neurol Neurosurg Psychiatry 2001;70(Suppl 1):i12–i16 (b) Effect of time to thrombolysis on favourable outcomes (mRS or 1) based on pooled analysis of thromoblysis trials With permission from Elsevier; Hacke W, Donnan G, Fieschi C, et al Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS and NINDS rt-PA stroke trials Lancet 2004;363:768–774 An important aspect of delivering thrombolysis is coordination and streamlining of stroke pathways to ensure rapid triage and assessment of patients arriving in accident and emergency, and fast access to CT scanning This could be facilitated by having a specialized “brain attack” team, alerted in advance by paramedics as to the arrival of a stroke patient potentially suitable for thrombolysis Once intracranial hemorrhage has been excluded, and provided there are not extensive early ischemic changes, r-tPA can be administered in the emergency room, with subsequent transfer to a stroke unit for intensive monitoring Even in centers where thrombolysis services are more established and the public well-educated about stroke as a medical emergency, thrombolysis rates are less than 10% of all strokes presenting to hospital (Nadeau et al 2005) In addition to improving the organization of stroke services, an alternative approach to increasing the thrombolysis rate would be to extend the therapeutic time window In some centers, thrombolytic treatment is being guided by more sophisticated imaging techniques using CT or MRI to assess the mismatch between areas of perfusion and established ischemia, which is believed to reflect penumbral tissue A small pilot study showed that thrombolysis might still be beneficial overall beyond 3 h if salvageable tissue can be demonstrated (Hacke et al 2005) Other approaches include intra-arterial thrombolysis and modulating the ischemic cascade using neuroprotective agents discussed later 64 A Hassan Table 7.1. Inclusion and exclusion criteria for acute stroke thrombolysis Safe Implementation of Thrombolysis in Stroke MOnitoring STudy (SITS-MOST protocol) Inclusion criteria • Age 18–80 years • Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition, gaze, vision and/or neglect Ischaemic stroke is defined as an event characterised by sudden onset of acute focal neurological deficit, presumed to be caused by cerebral ischaemia, after CT scan exclusion of haemorrhage • Onset of symptoms within 3 h prior to initiation of thrombolysis treatment • Stroke symptoms present for at least 30 min and has not significantly improved before treatment Symptoms must be distinguishable from an episode of generalized ischaemia (i.e., syncope), seizure, or migraine disorder • Patients are willing to receive thrombolysis treatment and to give informed consent with regard to retrieval of data and follow up procedures, according to the regulations in participating countries • Willingness and ability to comply with the study protocol Exclusion criteria The cerebral CT exclusion criteria are: • Evidence of intracranial haemorrhage (ICH) on the CT-scan The general exclusion criteria are: • Symptoms of ischaemic attack began more than 3 h prior to infusion start or when time of symptom onset is unknown • Minor neurological deficit or symptoms rapidly improving before start of infusion • Severe stroke as assessed clinically (e.g., NIHSS>25) and/or by appropriate imaging techniques • Seizure at onset of stroke • Symptoms suggestive of subarachnoid haemorrhage, even if the CT scan is normal • Administration of heparin within the previous 48 h and a thromboplastin time exceeding the upper limit of normal for laboratory • Patients with any history of prior stroke and concomitant diabetes • Prior stroke within the last 3 months • Platelet count of below 100,000/mm3 • Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits • Blood glucose 400 mg/dl • Known hemorrhagic diathesis • Patients receiving oral anticoagulants, e.g., warfarin • Manifest or recent severe or dangerous bleeding • Known history of or suspected intracranial haemorrhage • Suspected subarachnoid hemorrhage or condition after subarachnoid haemorrhage from aneurysm • Any history of central nervous system damage (i.e., neoplasm, aneurysm, intracranial or spinal surgery) • Haemorrhagic retinopathy, e.g., in diabetes (vision disturbances may indicate haemorrhagic retinopathy) • Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g., subclavian vein) • Bacterial endocarditis, pericarditis • Acute pancreatitis • Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformation • Neoplasm with increased bleeding risk • Severe liver disease including hepatic failure, cirrhosis, portal hypertension, oesophageal varices and active hepatitis • Major surgery or significant trauma in past 3 months Intra-Arterial Thrombolysis Intra-arterial thrombolysis has been shown to be effective in treating proximal middle cerebral artery occlusion up to 6 h using pro-urokinase (Furlan et al 1999), but requires superselective angiography, and is therefore available in few centers In our experience, intra-arterial thrombolysis probably has a greater role to play in acute progressive basilar artery occlusion Patients with this condition usually present with brainstem or cerebellar signs in a step-wise deteriorating manner The condition may not immediately be recognized, with patients mistakenly diagnosed with meningoencephalitis, especially if they have fever Patients are often transferred to ITU requiring intubation and ventilation because of deep coma or respiratory failure Initial CT scans may be normal, and the diagnosis requires a high index of clinical suspicion, as patients may not be well 7. Recent Advances in the Management of Acute Ischemic Stroke enough for MR studies Basilar artery occlusion has a high mortality (up to 90%), and diagnostic angiography, followed by local thrombolysis may be offered up to 24 h after onset, especially if there are signs of progression Observational studies suggest reduced morbidity and mortality with successful basilar artery recannalization, although some survivors may remain locked-in and dependent (Berg-Dammer et al 2000) Neuroprotection Specific pharmacological interventions have been tested which might limit infarct size However, in humans the results from a number of large phase III trials have been disappointing, with some agents causing harm This may reflect our limited understanding at present of the key events in cerebral ischemia at the molecular level, or the design of human trials A further concern centers on the ability of these drugs to target the ischemic penumbra, given the lack of cerebral blood flow The lack of success was typified by the agent NXY-059 (cerovive), which has free radical trapping properties It has been shown to reduce infarct size in animal models and in a Phase III study there was a statistically significant reduction in disability compared to placebo, as measured by the modified Rankin scale However, a second larger study was convincingly negative (Shuaib et al 2007) Similarly, clinical trials in man examining the role of intravenous magnesium as a neuroprotective agent have been disappointing (Muir et al 2004) Intriguingly, a small retrospective study found that patients randomized to statin withdrawal following acute ischemic stroke had larger infarct volumes and increased risk of death or dependency compared to those who were left on it in the acute phase (Blanco et al 2007) This study highlights potential neuroprotective properties of these agents, although clearly further work is needed Progressive Neurological Deterioration Once cerebral ischemia is established, patients may develop progressive symptoms leading to neurological deterioration, requiring ITU referral for supportive treatment including ventilation 65 Overall it is felt that the prognosis of stroke patients requiring ventilation is not as poor as it was once thought to be (Steiner et al 1997) There are a number of specific situations where ITU-supportive treatment and stabilization may facilitate further intervention Cerebellar and basilar artery thrombosis may cause localized edema and brainstem compression or hydrocephalus by obstruction of the fourth ventricle This is best managed by neurosurgically A further important cause of progressive symptoms is malignant middle cerebral artery infarction Clinically, patients present with typical MCA territory ischemia and there may be an interval where the patient is stable However, after 24 h there is development of severe cytotoxic edema, causing swelling of the affected hemisphere and tentorial brain herniation, recognized by pupil dilation and reduced conscious level (Fig. 7.2a–c) The condition usually affects younger patients, as it seems older patients are protected to some extent from the rapid increase in intracranial pressure by pre-existing cerebral atrophy The management of malignant MCA infarction has been controversial and neurosurgeons have been reluctant to offer decompressive craniectomy However, mortality is over 80% with conservative medical management alone (mannitol, ventilation, and sedation) A recent meta-analysis of three small, randomized controlled trials has shown that early decompressive craniectomy in stroke reduced mortality from malignant MCA syndrome to 70% stenosis, as a highly effective intervention A smaller, but still potentially worthwhile effect was seen in patients with mid-range stenosis 50–70% (Rothwell et al 2004), if surgery was carried out quickly, although this is not a widespread practice These findings have important implications with respect to arranging urgent investigations (carotid duplex) for stroke and deciding which patients with TIAs should be admitted to hospital for fast-tracking of tests Recently, scoring systems such as a simple ABCD (Department of Health 2005) (age, blood pressure, clinical features, duration of symptoms and presence of diabetes mellitus) score developed by Rothwell and colleagues have shown promise in prioritizing demands on limited resources (Johnston et al 2007) References Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, Colman PG, Chambers BR, Davis SM (2003) Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome Stroke 34:2208–2214 Berg-Dammer E, Felber SR, Henkes H, Nahser HC, Kuhne D (2000) Long-term outcome after local 7. Recent Advances in the Management of Acute Ischemic Stroke intra-arterial fibrinolysis of basilar artery thrombosis Cerebrovasc Dis 10:183–188 Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Dávalos A, Castillo J (2007) Statin treatment withdrawal in ischemic stroke: a controlled randomized study Neurology 69:904–910 Bonita R (1992) Epidemiology of stroke Lancet 339:342–344 Chen ZM, Sandercock P, Pan HC, Counsell C, Collins R, Liu LS, Xie JX, Warlow C, Peto R (2000) Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial On behalf of the CAST and IST collaborative groups Stroke 31:1240–1249 Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S (1999) Recombinant tissuetype plasminogen activator (Alteplase) for ischemic stroke to hours after symptom onset The ATLANTIS Study: a randomized controlled trial Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke JAMA 282:2019–2026 Clark WM, Albers GW, Madden KP, Hamilton S (2000) The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebocontrolled, multicenter study Thrombolytic therapy in acute ischemic stroke study investigators Stroke 31:811–816 Coull AJ, Lovett JK, Rothwell PM (2004) Population based study of early risk of stroke after transient ischemic attack or minor stroke: implications for public education and organisation of services BMJ 328:326 Department of Health (2005) Reducing brain damage: Faster access to better stroke care National Audit Office Report Furlan M, Marchal G, Viader F, Derlon JM, Baron JC (1996) Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra Ann Neurol 40:216–226 Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F (1999) Intra-arterial prourokinase for acute ischemic stroke The PROACT II study: a randomized controlled trial Prolyse in acute cerebral thromboembolism JAMA 282:2003–2011 Georgiadis D, Schwarz S, Aschoff A, Schwab S (2002) Hemicraniectomy and moderate hypothermia in patients with severe ischemic stroke Stroke 33:1584– 1588 Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, Bamford JM, James OF, Alberti KG (2007) Glucose-potassium-insulin infu- 67 sions in the management of post-stroke hyperglycaemia: the UK glucose insulin in stroke trial (GIST-UK) Lancet Neurol 6:397–406 Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Hoxter G, Mahagne MH (1995) Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke The European Cooperative Acute Stroke Study (ECASS) JAMA 274:1017–1025 Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P (1998) Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischemic stroke (ECASS II) Second European-Australasian acute stroke study investigators Lancet 352:1245–1251 Hacke W, Kaste M, Bogousslavsky J, Brainin M, Chamorro A, Lees K, Leys D, Kwiecinski H, Toni P, Langhorne P, Diener C, Hennerici M, Ferro J, Sivenius J, Gunnar N, Bath P, Olsen TS, Gugging M (2003) European stroke initiative recommendations for stroke managementupdate 2003 Cerebrovasc Dis 16:311–337 Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S (2004) Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials Lancet 363:768–774 Hacke W, Albers G, Al Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S (2005) The desmoteplase in acute ischemic stroke trial (DIAS): a phase II MRIbased 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase Stroke 36:66–73 Hajat C, Hajat S, Sharma P (2000) Effects of poststroke pyrexia on stroke outcome : a meta-analysis of studies in patients Stroke 31:410–414 Hakim AM (1987) The cerebral ischemic penumbra Can J Neurol Sci 14:557–559 Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, Sidney S (2007) Validation and refinement of scores to predict very early stroke risk after transient ischemic attack Lancet 369:283–292 Kogure T, Kogure K (1997) Molecular and biochemical events within the brain subjected to cerebral ischemia (targets for therapeutical intervention) Clin Neurosci 4:179–183 Langhorne P, Tong BL, Stott DJ (2000) Association between physiological homeostasis and early recovery after stroke Stroke 31:2518–2519 Lovett JK, Dennis MS, Sandercock PA, Bamford J, Warlow CP, Rothwell PM (2003) Very early risk of 68 stroke after a first transient ischemic attack Stroke 34:e138–e140 Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies Neurology 62:569–573 Muir KW, Lees KR, Ford I, Davis S (2004) Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial Lancet 363:439–445 Nadeau JO, Shi S, Fang J, Kapral MK, Richards JA, Silver FL, Hill MD (2005) TPA use for stroke in the Registry of the Canadian stroke network Can J Neurol Sci 32:433–439 National Stroke Strategy, Department of Health (2007) http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/ DH_081062 Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ (2004) Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery Lancet 363:915–924 Rothwell PM, Giles MF, Chandratheva A, Marquardt L, Geraghty O, Redgrave JN, Lovelock CE, Binney LE, Bull LM, Cuthbertson FC, Welch SJ, Bosch S, Alexander FC, Silver LE, Gutnikov SA, Mehta Z (2007) Early use of Existing Preventive Strategies for Stroke (EXPRESS) study Effect of urgent treatment of transient ischemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison Lancet 370:1432–1442 Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, Einhaupl K, Diener HC, Dominiak P (2003) The ACCESS Study: evaluation of Acute Candesartan Cilexetil therapy in stroke survivors Stroke 34:1699–1703 A Hassan Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, Diener HC, Ashwood T, Wasiewski WW, Emeribe U (2007) SAINT II Trial Investigators NXY-059 for the treatment of acute ischemic stroke N Engl J Med 357:562–571 Steiner T, Mendoza G, De Georgia M, Schellinger P, Holle R, Hacke W (1997) Prognosis of stroke patients requiring mechanical ventilation in a neurological critical care unit Stroke 28:711–715 Stroke Unit Trialists’ Collaboration (2000) Organised inpatient (stroke unit) care for stroke Cochrane Database Syst Rev 2:CD000197 Sulter G, Elting JW, Langedijk M, Maurits NM, De Keyser J (2003) Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit: a randomized pilot study Stroke 34:101–104 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke N Engl J Med 333:1581–1587 Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, Amelink GJ, Schmiedeck P, Schwab S, Rothwell PM, Bousser MG, van der Worp HB, Hacke W, DECIMAL, DESTINY, and HAMLET investigators (2007) Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials Lancet Neurol 6:215–222 Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G, SITS-MOST investigators (2007) Thrombolysis with alteplase for acute ischemic stroke in the Safe Implementation of thrombolysis in stroke-monitoring study (SITS-MOST): an observational study Lancet 369:275-282 ... of Brainstem Death 10 5 Paul G Murphy Chapter 13 Death and Donation in Critical Care: Management of Deceased Organ Donation 11 3 Paul G Murphy Chapter 14 Imaging the Brain-Injured Patient... General supportive care includes avoidance of aspects that allow a hematoma to expand through loss or dilution of platelets or coagulation factors Hypothermia, hypocalcemia, and administration... Young et al 2003) As such, ICP- and CPP-targeted therapy have now become an accepted standard of care in head injury management The 2007 Brain Trauma Foundation Guidelines (Brain Trauma Foundation